Cartilage degradation, due to an imbalance between anabolic and catabolic rate of chondrocyte metabolism, is the main feature of Osteoarthritis (OA). To date, OA is mainly treated with Non Steroidal Anti-Inflammatory Drugs (NSAIDs), in order to reduce arthritis-related symptoms. In the last decades an increasing number of patients have started to use supplements, such as Glucosamine (GlcN) and chondroitin sulfate, as potential chondroprotective agents. Several in vivo clinical trials as well as in vitro experiments have been performed reporting inconsistent outcomes. Previously, in our lab we analyzed the anabolic effects of GlcN and its N-acetyl-phenylalanine derivative (NAPA) in a rabbit OA model, finding that intra-articular administration of GlcN and NAPA was very effective in reducing cartilage changes in injured rabbit knee. GlcN and NAPA intra-articular administration allows higher concentrations to be reached in the joints compared to oral administration, thus providing an explanation for the ability of both molecules to interfere with OA progression. We also studied the effects of GlcN and NAPA on inflammatory pathways, finding that both molecules can interfere with MAP kinase and NF-kB pathways, by interfering with IKK activity. Finally, we studied the effectiveness of GlcN and NAPA one the biosynthetic activity and hence the matrix production of human primary chondrocytes cultured in micromasses, which represent a good tridimensional culture model. We explored the ability of GlcN and NAPA to stimulate the synthesis of collagen type II (Coll II), Aggrecan (ACAN) and Small Leucine-Rich Proteoglycans (SLRPs). After 6 weeks, micromasses stimulated with GlcN + NAPA still showed a large amount of ECM compared to untreated cells. Moreover, Collagen type II was more abundant and better organized compared to that produced by untreated cells. Finally, cells resulted viable in both treated and untreated micromasses, even if in the middle of untreated micromasses, few dead cells were observed, whereas in the treated micromasses only viable cells and cells completely surrounded by ECM were detected.
Glucosamine and its peptidyl-derivative NAPA: novel therapeutic strategy for chondrocytes matrix remodeling / Cocchiola, Rossana; Lopreiato, Mariangela; Politi, Laura; Scandurra, Roberto; SCOTTO D'ABUSCO, Anna. - STAMPA. - (2017). (Intervento presentato al convegno 6th FEBS Advanced Lecture Course FEBS - MPST 2017 Matrix Pathobiology, Signaling and Molecular Targets tenutosi a Spetses, Greece).
Glucosamine and its peptidyl-derivative NAPA: novel therapeutic strategy for chondrocytes matrix remodeling
Rossana Cocchiola;Mariangela Lopreiato;Laura Politi;Roberto Scandurra;Anna Scotto d'Abusco
2017
Abstract
Cartilage degradation, due to an imbalance between anabolic and catabolic rate of chondrocyte metabolism, is the main feature of Osteoarthritis (OA). To date, OA is mainly treated with Non Steroidal Anti-Inflammatory Drugs (NSAIDs), in order to reduce arthritis-related symptoms. In the last decades an increasing number of patients have started to use supplements, such as Glucosamine (GlcN) and chondroitin sulfate, as potential chondroprotective agents. Several in vivo clinical trials as well as in vitro experiments have been performed reporting inconsistent outcomes. Previously, in our lab we analyzed the anabolic effects of GlcN and its N-acetyl-phenylalanine derivative (NAPA) in a rabbit OA model, finding that intra-articular administration of GlcN and NAPA was very effective in reducing cartilage changes in injured rabbit knee. GlcN and NAPA intra-articular administration allows higher concentrations to be reached in the joints compared to oral administration, thus providing an explanation for the ability of both molecules to interfere with OA progression. We also studied the effects of GlcN and NAPA on inflammatory pathways, finding that both molecules can interfere with MAP kinase and NF-kB pathways, by interfering with IKK activity. Finally, we studied the effectiveness of GlcN and NAPA one the biosynthetic activity and hence the matrix production of human primary chondrocytes cultured in micromasses, which represent a good tridimensional culture model. We explored the ability of GlcN and NAPA to stimulate the synthesis of collagen type II (Coll II), Aggrecan (ACAN) and Small Leucine-Rich Proteoglycans (SLRPs). After 6 weeks, micromasses stimulated with GlcN + NAPA still showed a large amount of ECM compared to untreated cells. Moreover, Collagen type II was more abundant and better organized compared to that produced by untreated cells. Finally, cells resulted viable in both treated and untreated micromasses, even if in the middle of untreated micromasses, few dead cells were observed, whereas in the treated micromasses only viable cells and cells completely surrounded by ECM were detected.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.